The existence of varying quantities of enkephalin-like peptides in adrenal glands of cow, human, dog, guinea pig and rat has been demonstrated by a radioimmunoassay technique. The concentrations detected are higher in dog and cow than in guinea pig and rat. In every species, a large proportion of the total immunoreactivity is present as high molecular weight form; furthermore, these high molecular weight forms are concentrated primarily in chromaffin granules. In order to explore the physiological role of enkephalin-like peptides in adrenal, in vivo secretion of these peptides from dog adrenal was studied. Stimulation of the splanchnic nerves resulted in a voltage-dependent increase in plasma levels of the enkephalin-like peptides; their secretion was increased after injections of methacholine and morphine and these effects were blocked by atropine and naloxone, respectively. We will continue to study the physiological regulation of the secretion of these enkephalin-like peptides from the adrenal gland.